Safety and Tolerability of Metformin in People With Tuberculosis (TB) and Human Immunodeficiency Virus (HIV)

Summary

The METHOD study will examine whether adding metformin to standard antibiotic treatment for tuberculosis (TB) in people with HIV is safe and well tolerated. The study will also test if adding metformin clears the infection more quickly and with less lung damage. When enrolled, participants will have an equal chance of being in the group that takes standard TB medicines alone or in the group that also takes metformin. Participants will have a chance to be put on either: 1) standard TB medicines (isoniazid, rifampicin, ethambutol and pyrazinamide for two months, continuing isoniazid and rifampin for four more months) only; or 2) the same standard TB medicines plus metformin. Participants randomized to the metformin arm will take metformin for eleven weeks, starting one week after starting the standard TB medicines. In addition to monitoring for side effects, all participants will have studies of drug levels and lung and immune function.

Conditions

• Tuberculosis
• Pulmonary Tuberculosis
• HIV Coinfection

Interventions

DRUG

Isoniazid

Isoniazid, dose prescribed by participant's physician, will be taken by mouth daily. Isoniazid, is in a combination pill pack with the other standard ATT medications.

DRUG

Rifampicin

Rifampicin, dose prescribed by participant's physician, will be taken by mouth daily. Rifampicin is in a combination pill pack with the other standard ATT medications.

DRUG

Ethambutol

Ethambutol, dose prescribed by participant's physician, will be taken by mouth daily. Ethambutol is in a combination pill pack with the other standard ATT medications.

DRUG

Pyrazinamide

Pyrazinamide, dose prescribed by participant's physician, will be taken by mouth daily. Pyrazinamide is in a combination pill pack with the other standard ATT medications.

DRUG

Metformin hydrochoride

Metformin hydrochloride 500 mg tablet once daily starting one week after the initiation of TB treatment, then increasing to twice daily through study week-12 (11 weeks total metformin treatment).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  collaborator NIH

• Aurum Institute

  collaborator OTHER

• A*STAR Infectious Diseases Labs

  collaborator INDUSTRY

• University of Cape Town

  collaborator OTHER

• Wits Health Consortium (Pty) Ltd

  collaborator OTHER

• University of Massachusetts, Worcester

  lead OTHER

Principal Investigators

• Robert S Wallis, MD, FIDSA · Aurum Institute

• Hardy Kornfeld, MD · The University of Massachusetts Chan Medical School

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-08-26

Primary Completion

2025-04-29

Completion

2025-08-15

FDA Drug

Yes

Countries

• South Africa

Study Locations